Activation of the p42 mitogen-activated protein kinase pathway inhibits Cdc2 activation and entry into M-phase in cycling Xenopus egg extracts.
We have added constitutively active MAP kinase/ERK kinase (MEK), an activator of the mitogen-activated protein kinase (MAPK) signaling pathway, to cycling Xenopus egg extracts at various times during the cell cycle. p42MAPK activation during entry into M-phase arrested the cell cycle in metaphase, as has been shown previously. Unexpectedly, p42MAPK activation during interphase inhibited entry into M-phase. In these interphase-arrested extracts, H1 kinase activity remained low, Cdc2 was tyrosine phosphorylated, and nuclei continued to enlarge. The interphase arrest was overcome by recombinant cyclin B. In other experiments, p42MAPK activation by MEK or by Mos inhibited Cdc2 activation by cyclin B. PD098059, a specific inhibitor of MEK, blocked the effects of MEK(QP) and Mos. Mos-induced activation of p42MAPK did not inhibit DNA replication. These results indicate that, in addition to the established role of p42MAPK activation in M-phase arrest, the inappropriate activation of p42MAPK during interphase prevents normal entry into M-phase.
Bitangcol
J C
JC
Molecular Mechanisms of Growth Control Group, Department of Cell Biology and Anatomy, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
Chau
A S
AS
Stadnick
E
E
Lohka
M J
MJ
Dicken
B
B
Shibuya
E K
EK
D000595:Amino Acid Sequence; D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D002457:Cell Extracts; D019926:Cyclin B / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology; D003513:Cycloheximide / Q000494:pharmacology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D048369:MAP Kinase Kinase 1; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases; D008938:Mitosis / Q000502:physiology*; D008969:Molecular Sequence Data; D010063:Ovum; D010766:Phosphorylation; D006656:Protamine Kinase / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology; D017231:Proto-Oncogene Proteins c-mos / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism; D014981:Xenopus
D002457:Cell Extracts; D019926:Cyclin B; D004791:Enzyme Inhibitors; D005419:Flavonoids; D011500:Protein Synthesis Inhibitors; D014443:Tyrosine; D003513:Cycloheximide; D011505:Protein-Tyrosine Kinases; D006656:Protamine Kinase; D017346:Protein Serine-Threonine Kinases; D017231:Proto-Oncogene Proteins c-mos; D016203:CDC2 Protein Kinase; D019950:Mitogen-Activated Protein Kinase 1; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one